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Abstract
Annual Review of Pharmacology and Toxicology
Vol. 47: 443-467 (Volume publication date February 2007)
(doi:10.1146/annurev.pharmtox.47.120505.105359)
First published online as a Review in Advance on August 29, 2006
mTOR Pathway as a Target in Tissue Hypertrophy

Chung-Han Lee,1,2 ­Ken Inoki,1,2 and­Kun-Liang Guan1,2,3­
1Life Science Institute, 2Department of Biological Chemistry, and 3Institute of Gerontology, University of Michigan, Ann Arbor, Michigan 48109; email: , ,

Abstract Recent work has shown that the mTOR (mammalian target of rapamycin) pathway is an integral cell growth regulator. The mTOR pathway involves two functional complexes, TORC1 and TORC2, which have been defined by both their association with raptor or rictor, respectively, and their sensitivity to short-term rapamycin inhibition. Loss of tumor suppressors TSC1 or TSC2 leads to aberrant activation of TORC1, which has been implicated in the control of cell size. As a result, both physiologic and pathologic tissue hypertrophy are associated with TORC1 activation. Some clinical examples include skeletal and cardiac muscle hypertrophy, vascular restenosis, and compensatory nephrotic hypertrophy. Clarification of the mTOR pathway may lead to increased understanding of both the etiology and consequences of aberrant cell size regulation. This review covers some of the biochemical regulation of the mTOR pathway that may be important to the regulation of cell size, and it will present several potential clinical applications where the control of cell size may be biologically significant.

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Authors:
Chung-Han Lee
Ken Inoki
Kun-Liang Guan
Keywords:
rapamycin
TSC
AKT
cancer
muscle

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